Ongoing | Non-malignant Hematology, Neurological Disorders, and Other Indications Accelerated Approvals
This listing includes accelerated approvals (AAs) for non-malignant hematological, neurological, and other disorder indications that have postmarketing requirement(s) for ongoing clinical trial(s) to verify clinical benefit.
Please refer to Drugs@FDA for the latest approvals and prescribing information for specific products. See Postmarket Requirements and Commitments for the status of specific requirements.
Visit Accelerated Approvals for listings of ongoing, verified clinical benefit, and withdrawn infectious diseases and non-malignant hematological, neurological, and other disorder indications accelerated approvals.
Indications may remain on this page until FDA updates product labeling or publishes a Federal Register notice regarding a change in status.
Ongoing 1 Heme/Neuro/Other Accelerated Approvals
| Drug Name | Accelerated Approval Indication | Accelerated Approval Date | AA PMR | Original Projected Completion Date 2 |
|---|---|---|---|---|
| Vonjo (pacritinib) | For the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 x 109/L | 2/28/2022 | PMR 4154-1: Conduct a randomized, controlled trial to verify and describe the clinical benefit of Vonjo in adults with intermediate-1, intermediate-2 or high-risk myelofibrosis (MF) [as defined by the Dynamic International Prognostic Scoring System (DIPSS), including primary MF, post-polycythemia vera and post-essential thrombocythemia MF] with platelet counts of less than 50 x 109/L. The co-primary efficacy endpoints are the proportion of patients achieving =35% spleen volume reduction as measured by magnetic resonance imaging or computed tomography imaging; and the proportion of patients achieving a =50% reduction in modified total symptom score (mTSS) [as defined by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF TSS 2.0) that excludes the “tiredness” component] from baseline through 24 weeks of therapy. Longterm safety outcomes include the risks for bleeding, thrombosis, infections, major adverse cardiac events, secondary malignancies, and survival. | 6/30/2026 |
| Skysona (elivaldogene autotemcel) | Indicated to slow the progression of neurologic dysfunction in boys 4-17 years of age with early, active cerebral adrenoleukodystrophy (cald) | 9/16/2022 | PMR 1: Follow all subjects who received elivaldogene autotemcel in Studies ALD-102 and ALD-104 to assess event-free survival (i.e., alive without Major Functional Disability (MFD) or need for hematopoietic stem cell transplant (HSCT)) for a minimum of ten years following administration of elivaldogene autotemcel. | 7/31/2032 |
| Skysona (elivaldogene autotemcel) | Indicated to slow the progression of neurologic dysfunction in boys 4-17 years of age with early, active cerebral adrenoleukodystrophy (cald) | 9/16/2022 | PMR 2: Investigate event-free survival for at least five years post-treatment in 24 boys with more advanced early active, cerebral adrenoleukodystrophy (CALD) [(based on baseline Loes scores and Neurologic Function Score (NFS)] who will be newly treated with elivaldogene autotemcel (SKYSONA) | 12/31/2038 |
| Oxbryta (tablets; voxelotor) | For the treatment of sickle cell disease in adults and pediatric patients 4 years of age and older | 12/17/2021 | PMR 3746-1: Complete Study GBT440-032: the ongoing Phase 3, randomized, double-blind, placebo-controlled trial in pediatric patients (age 2 years to <15 years) with Sickle Cell Disease (HOPE Kids 2). Expected enrollment of approximately 224 patients (age 2 years to <15 years) with at least 15 patients from age 2 years to < 4 years of age. Include patients with baseline hemoglobin of less than 6 g/dL. The primary endpoint is change from baseline at 24 weeks in time averaged maximum of mean velocity (TAMMV) arterial cerebral blood flow as measured by transcranial doppler (TCD). The secondary endpoint is change from baseline in TCD flow velocity at Week 48 and Week 96. | 9/30/2026 |
| Oxbryta (tablets for oral suspension; voxelotor) | For the treatment of sickle cell disease in adults and pediatric patients 4 years of age and older | 12/17/2021 | PMR 4190-1: Complete Study GBT440-032: the ongoing Phase 3, randomized, double-blind, placebo-controlled trial in pediatric patients (age 2 years to <15 years) with Sickle Cell Disease (HOPE Kids 2). Expected enrollment of approximately 224 patients (age 2 years to <15 years) with at least 15 patients from age 2 years to < 4 years of age. Include patients with baseline hemoglobin of less than 6 g/dL. The primary endpoint is change from baseline at 24 weeks in time averaged maximum of mean velocity (TAMMV) arterial cerebral blood flow as measured by transcranial doppler (TCD). The secondary endpoint is change from baseline in TCD flow velocity at Week 48 and Week 96. | 9/30/2026 |
| Tarpeyo (budesonide) | To reduce proteinuria in adults with primary immunoglobulin a nephropathy (igan) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (upcr) ≥ 1.5 g/g | 12/15/2021 | PMR 4203-1: Conduct a randomized, double-blind, placebo-controlled trial to describe and verify the clinical benefit of budesonide for the treatment of IgA nephropathy. The trial should be adequately powered and of sufficient duration to detect a treatment effect on the endpoint that will be used to describe and verify the clinical benefit. | 7/31/2023 |
| Voxzogo (vosoritide) | To increase linear growth in pediatric patients with achondroplasia who are 5 years of age and older with open epiphyses | 11/19/2021 | PMR 4134-1: Conduct an open-label, external-controlled trial in subjects with achondroplasia (ACH) 5 years of age and older with open epiphyses to measure the effect of vosoritide on final adult height. The trial should also evaluate disproportionality and bone age as secondary endpoints. The safety endpoints related to the drug (e.g., blood pressure) or to the disease itself that may improve or worsen with long-term treatment (e.g.,neurological complications, bone deformities, sleep apnea) should also be included. The total exposure to vosoritide for each patient should be sufficient to meet the study’s stated objectives. The vosoritide-treated trial population should include subjects who are already enrolled and treated with vosoritide in Studies 111-2024 /2055, and 111-3016 /3027 and/or treatment-naïve subjects with a genetically confirmed ACH diagnosis. | 8/31/2025 |
| Aduhelm (aducanumab-avwa) | For the treatment of alzheimer’s disease | 6/7/2021 | PMR 3971-1: In order to verify the clinical benefit of aducanumab, conduct a randomized, controlled trial to evaluate the efficacy of aducanumab-avwa compared to an appropriate control for the treatment of Alzheimer’s disease. The trial should be of sufficient duration to observe changes on an acceptable endpoint in the patient population enrolled in the trial. | 2/28/2030 |
| Amondys 45 (casimersen) | For the treatment of duchenne muscular dystrophy (dmd) in patients who have a confirmed mutation of the dmd gene that is amenable to exon 45 skipping | 2/25/2021 | PMR 4005-1: In order to verify the clinical benefit of casimersen, complete Study 4045301 (Essence), A Double-Blind, Placebo-Controlled, Multicenter Study with an Open-Label Extension to Evaluate the Efficacy and Safety of SRP-4045 and SRP-4053 in Patients with Duchenne Muscular Dystrophy. The study includes a randomized, double-blind, placebo-controlled period of 96-weeks and concludes after an open label extension period to 144 weeks. The primary endpoint will be the 6-minute walk test. | 10/31/2024 |
| Viltepso (viltolarsen) | For the treatment of duchenne muscular dystrophy (dmd) in patients who have a confirmed mutation of the dmd gene that is amenable to exon 53 skipping | 8/12/2020 | PMR 3895-1: In order to verify the clinical benefit of viltolarsen, complete Study NS065/NCNP-01-301, “A Phase 3 Randomized, Double-blind, Placebocontrolled, Multi-center Study to Assess the Efficacy and Safety of Viltolarsen in Ambulant Boys with Duchenne Muscular Dystrophy.” The study will assess treatment with viltolarsen 80 mg/kg over 48 weeks. The primary endpoint will be Time to Stand. | 12/31/2024 |
| Vyondys 53 (golodirsen) | For the treatment of duchenne muscular dystrophy (dmd) in patients who have a confirmed mutation of the dmd gene that is amenable to exon 53 skipping | 12/12/2019 | PMR 3690-1: In order to verify the clinical benefit of golodirsen, complete Study 4045- 301, A Double-Blind, Placebo Controlled, Multicenter Study With an Open- Label Extension to Evaluate the Efficacy and Safety of SRP-4045 and SRP-4053 in Patients With Duchenne Muscular Dystrophy. The study includes a randomized, double-blind, placebo-controlled period of 96 weeks, and concludes after an open-label extension period to 144 weeks. The primary endpoint will be the 6-minute walk test. | 10/30/2024 |
| Oxbryta (tablets; voxelotor) | For the treatment of sickle cell disease in adults and pediatric patients 12 years of age and older | 11/25/2019 | PMR 3746-1: Complete Study GBT440-032: the ongoing Phase 3, randomized, doubleblind, placebo-controlled trial in pediatric patients (age 2 years to < 15 years) with Sickle Cell Disease (HOPE Kids 2). Expected enrollment of approximately 224 patients (age 2 years to < 15 years) with at least 15 patients from age 2 years to < 4 years of age. Include patients with baseline hemoglobin of less than 6 g/dL. The primary endpoint is change from baseline at 24 weeks in time averaged maximum of mean velocity (TAMMV) arterial cerebral blood flow as measured by transcranial Doppler (TCD). The secondary endpoint is change from baseline in TCD flow velocity at Week 48 and Week 96. | 9/30/2026 |
| Galafold (migalastat) | For the treatment of adults with a confirmed diagnosis of fabry disease and an amenable galactosidase alpha gene (gla) variant based on in vitro assay data | 8/10/2018 | PMR 3412-1: A randomized, double-blind, placebo-controlled clinical trial to verify and describe the clinical benefit of Galafold (migalastat) in patients with Fabry disease. The trial will evaluate the efficacy and pharmacodynamic effects (e.g., on plasma lyso-Gb3, alpha-Gal A enzyme activity) of Galafold (migalastat) in patients with a confirmed diagnosis of Fabry disease and amenable, diseasecausing GLA variants. The trial should be of sufficient duration to observe clinically meaningful changes in Fabry-related symptoms in the intended patient population. | 8/31/2026 |
| Galafold (migalastat) | For the treatment of adults with a confirmed diagnosis of fabry disease and an amenable galactosidase alpha gene (gla) variant based on in vitro assay data | 8/10/2018 | PMR 3412-2: A prospective, longitudinal, observational study to evaluate the efficacy and pharmacodynamic effects of Galafold (migalastat) in patients with a confirmed diagnosis of Fabry disease and amenable, disease-causing GLA variants. The study will collect, analyze, and compare long-term data on clinical outcomes (major renal, cardiac, and cerebrovascular events) and pharmacodynamic changes (e.g., in WBC alpha-Gal A enzyme activity, plasma lyso-Gb3, serum and urine creatinine, eGFR, urine protein, urine albumin) in treated and untreated patients with Fabry disease and amenable GLA variants. The data will be used for the verification and description of the clinical benefit of Galafold (migalastat) in patients with Fabry disease and amenable GLA variants. | 4/30/2031 |
| Andexxa (coagulation factor xa (recombinant), inactivated-zhzo) | For patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding | 5/3/2018 | PMR 1: Study-18-513: "A Phase 4 randomized trial of ANDEXXA in acute intracranial hemorrhage in patients receiving oral factor Xa inhibitors": This open-label, randomized trial will include at least 440 adult patients who developed acute intracranial hemorrhage following the treatment with rivaroxaban, apixaban, or edoxaban 15 hours or less prior to randomization. The enrolled patients will be administered ANDEXXA (high or low dose) or standard of care other than ANDEXXA according to 1:1 randomization scheme. To describe and verify the hemostatic effect of ANDEXXA, patients will be assessed with the National Institute of Health Stroke Scale and computed tomography or magnetic resonance imaging at 12-hours post- randomization. The trial assessments will also include evaluation of occurrence of the safety events of special interest, including but not limited to: stroke, transient ischemic event, acute myocardial infarction, deep vein thrombosis, pulmonary embolism, arterial systemic embolism, sudden death, and events suspicious for thrombosis, embolism, and ischemia, all to be observed at least 3 days for immediate occurrence and at least 30 days with weekly intervals for delayed occurrence. The assessments of the hemostatic effect will be made by an adjudication committee blinded to the treatment allocation. | 4/30/2023 |
| Exondys 51 (eteplirsen) | For the treatment of duchenne muscular dystrophy (dmd) in patients who have a confirmed mutation of the dmd gene that is amenable to exon 51 skipping | 9/19/2016 | PMR 3095-1: In order to verify the clinical benefit of eteplirsen, conduct a 2-year randomized, double-blind, controlled trial of eteplirsen in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping. Patients should be randomized to the approved dosage of eteplirsen (30 mg/kg weekly) or to a dosage that provides significantly higher exposure, e.g., 30 mg/kg daily. The primary endpoint will be the North Star Ambulatory Assessment. | 5/31/2021 |
| Ocaliva (obeticholic acid) | For the treatment of primary biliary cholangitis (pbc) in combination withursodeoxycholic acid (udca) in adults with an inadequate response to udca, or as monotherapy in adults unable to tolerate udca | 5/27/2016 | PMR 3057-1: A randomized, placebo-controlled clinical trial to evaluate the safety, efficacy and steady-state pharmacokinetics of OCALIVA (obeticholic acid) in patients with primary biliary cholangitis (PBC) with Child-Pugh Classes B and C hepatic impairment, including Child-Pugh Class C patients with varying levels of Model for End-Stage Liver Disease (MELD) scores. You may conduct this as a standalone trial or in a subset of patients in your confirmatory trial (PMR# 3057-3). | 4/30/2023 |
| Ocaliva (obeticholic acid) | For the treatment of primary biliary cholangitis (pbc) in combination withursodeoxycholic acid (udca) in adults with an inadequate response to udca, or as monotherapy in adults unable to tolerate udca | 5/27/2016 | PMR 3057-2: A randomized, placebo-controlled trial to evaluate the safety and efficacy of OCALIVA (obeticholic acid) used as monotherapy in patients with primary biliary cholangitis (PBC) who are intolerant of or non-responsive to ursodeoxycholic acid (UDCA). Enroll patients across all stages of PBC, by the Rotterdam criteria. You may conduct this as a standalone trial or in a subset of patients in your confirmatory trial (PMR # 3057-3). | 4/30/2023 |
| Ocaliva (obeticholic acid) | For the treatment of primary biliary cholangitis (pbc) in combination withursodeoxycholic acid (udca) in adults with an inadequate response to udca, or as monotherapy in adults unable to tolerate udca | 5/27/2016 | PMR 3057-3: A randomized, double-blind, placebo-controlled trial to verify and describe that OCALIVA (obeticholic acid) induced reductions in alkaline phosphatase and/or total bilirubin are associated with improvements in the composite clinical endpoint of progression to cirrhosis, death, transplant, decompensation events, and hepatocellular cancer. Your ongoing trial (747-302) should be revised to include patients across the spectrum of stages of primary biliary cholangitis (PBC), including patients with early, moderately advanced and advanced PBC by the Rotterdam criteria, and should be adequately powered to demonstrate benefit in each stage. | 4/30/2023 |
| Provayblue (methylene blue) | For the treatment of pediatric and adult patients with acquired methemoglobinemia | 4/8/2016 | PMR 3065-1: Design and conduct a study and provide the full final report and data sets to evaluate the safety and efficacy of ProvayBlue (methylene blue) for the treatment of methemoglobinemia. The minimal efficacy endpoints should include achieving a 50% reduction in methemoglobin within one hour of the first dose of ProvayBlue (methylene blue) in addition to normalization of the respiratory rate, heart rate and blood pressure within two hours of the first dose of ProvayBlue (methylene blue). | 9/30/2020 |
| Northera (droxidopa) | For the treatment of orthostatic dizziness, lightheadedness, or the “feeling that you are about to black out” in adult patients with symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure (parkinson's disease, multiple system atrophy,and pure autonomic failure), dopamine beta-hydroxylase deficiency, and non-diabetic autonomic neuropathy | 2/18/2014 | PMR 2129-2: A clinical trial of patients with symptomatic neurogenic orthostatic hypotension to assess sustained effects of droxidopa therapy. The trial design consists of a 3-month, open-label droxidopa treatment period, followed by a 3-month, randomized, double-blind, placebo controlled, withdrawal period. The primary endpoint will be time to treatment intervention. | 8/31/2021 |
| Elaprase (idursulfase) | Provides for additional safety and efficacy information for the treatment of patients with hunter syndrome 5 years of age and younger | 6/24/2013 | PMR 2792-1: To conduct a verification trial to describe clinical benefit attributable to Elaprase (idursulfase) in a cohort of Hunter syndrome patients 5 years of age and younger. At a minimum, this trial will assess longitudinal changes in anthropometric measures (i.e., length/height z-scores, annual growth velocity z-scores, weight z-scores) and the progression of skeletal deformities (i.e., joint stiffness, joint contractures) in children being treated with Elaprase (idursulfase). The growth parameters will be followed in these children for a minimum of 5 years from initiation of Elaprase (idursulfase) treatment or until they have reached at least 10 years of age, whichever is longer. The trials will monitor antibody response (binding, neutralizing, and IgE) at least every 6 months. Additionally, the trial will evaluate the relationship between development of immune tolerance and genetic mutations, endogenous enzyme activity level, and anthropometric measures. The trial may be conducted as a separate trial or as a sub-trial under a special protocol within the Hunter Outcome Survey. | 9/30/2022 |
| Elaprase (idursulfase) | Provides for additional safety and efficacy information for the treatment of patients with hunter syndrome 5 years of age and younger | 6/24/2013 | PMR 2792-2: To evaluate a prophylactic immune tolerance regimen in a cohort of Hunter syndrome patients treated with Elaprase (idursulfase) who are at high risk of developing persistent neutralizing antibody that could result in diminished clinical benefit. This immune tolerance regimen will be implemented before or concomitant with onset of therapy. The trial will monitor antibody status (binding, neutralizing, and IgE), urinary GAG, and hypersensitivity reactions in patients at regular intervals. Additionally, the trial will evaluate the relationship between development of immune tolerance and genetic mutations, endogenous enzyme activity level, and clinical outcome. Completion of this PMR is pending the outcome of an Advisory Committee Meeting and completion of PMR 3. | 9/30/2022 |
| Makena (hydroxyprogesterone caproate) | To reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth | 2/3/2011 | PMR 1722-1: To complete the clinical trial of hydroxyprogesterone caproate in women with a singleton pregnancy who had a previous spontaneous preterm birth (Protocol #17P-ES-003). | 12/31/2016 |
| Makena (hydroxyprogesterone caproate) | To reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth | 2/3/2011 | PMR 1722-2: To complete the clinical follow-up study (Protocol #17P-FU-004) of children born to women who participated in Protocol #17P-ES-003. | 10/31/2018 |
| Vigiv 3 (vaccinia immune globulin intravenous (human)) | Treatment and/or modification of the following conditions, which are complications resulting from smallpox vaccination: eczema vaccinatum progressive vaccinia severe generalized vaccinia vaccinia infections in individuals who have skin conditions such as burns, impetigo, varicella-zoster, or poison ivy; or in individuals who have eczematous skin lesions because of either the activity or extensiveness of such lesions aberrant infections induced by vaccinia virus that include its accidental implantation in eyes (except in cases of isolated keratitis), mouth, or other areas where vaccinia infection would constitute a special hazard. | 5/2/2005 | PMR 1: Work with the FDA, and other public agencies as appropriate, to design and implement a clinical study protocol to include VIGIV dose ranging, and conduct a study to describe the treatment and clinical course of patients receiving VIGIV for complications of vaccinia infection when such a study is feasible, due to the actual or impending widespread use of VIGIV. | |
| Proamatine (midodrine hydrochloride) | For the treatment of symptomatic orthostatic hypotension (oh) | 9/6/1996 | PMR 825-1: Applicant to conduct a Phase 4 study to confirm the clinical benefit of midodrine. Protocol drafts submitted at 7/18/1996 meeting. Protocols are 401, 402, and 403. | 3/31/2015 |
- 1. Ongoing" refers to accelerated approval (AA) applications that have not yet converted to full approval, and not to the status of the AA postmarketing requirement (PMR).
- 2. If multiple PMRs were required, the latest date is reported here. This date represents the original agreed-upon Final Study Report date and does not include any updated deadlines submitted by the Applicant.
- 3. This PMR does not have a target completion date as is dependent on when such a study is feasible, due to the actual or impending widespread use of VIGIV.